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    Summary
    EudraCT Number:2015-000246-34
    Sponsor's Protocol Code Number:MK7655A-014
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2021-02-08
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2015-000246-34
    A.3Full title of the trial
    A Phase III, Randomized, Double-Blind, Active Comparator-Controlled Clinical Trial to Study the Safety, Tolerability, and Efficacy of Imipenem/Cilastatin/Relebactam (MK-7655A) Versus Piperacillin/Tazobactam in Subjects with Hospital-Acquired Bacterial Pneumonia or Ventilator-Associated Bacterial Pneumonia.
    Studio clinico di fase III, randomizzato, in doppio cieco, controllato con farmaco attivo di confronto per valutare la sicurezza, la tollerabilit¿ e l¿efficacia di Imipenem/Cilastatina/Relebactam (MK7655A) verso Piperacillina/Tazobactam in pazienti affetti da polmonite batterica nosocomiale o associata a ventilazione meccanica.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    IMI/REL (MK-7655A) vs. PIP/TAZ in Treatment of Subjects with HABP/VABP.
    IMI/REL (MK-7655A) vs. PIP/TAZ nel trattamento di soggetti con HABP/VABP.
    A.3.2Name or abbreviated title of the trial where available
    IMI/REL (MK-7655A) vs. PIP/TAZ in Treatment of Subjects with HABP/VABP.
    IMI/REL (MK-7655A) vs. PIP/TAZ nel trattamento di soggetti con HABP/VABP.
    A.4.1Sponsor's protocol code numberMK7655A-014
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorMERCK SHARP & DOHME CORP. UNA SUSSIDIARIA DI MERCK & CO. INC.
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportMERCK SHARP & DOHME CORP. UNA SUSSIDIARIA DI MERCK
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationMSD Italia S.r.l.
    B.5.2Functional name of contact pointDivisione Ricerca Clinica
    B.5.3 Address:
    B.5.3.1Street AddressVia Fratelli Cervi, snc ¿ Centro Direzionale Milano Due ¿ Palazzo Canova
    B.5.3.2Town/ citySegrate (MI)
    B.5.3.3Post code20090
    B.5.3.4CountryItaly
    B.5.4Telephone number00390221018402
    B.5.5Fax number00390221018629
    B.5.6E-mailgcto.italy@merck.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameimipenem/cilastatin/relebactam
    D.3.2Product code MK-7655A
    D.3.4Pharmaceutical form Powder for solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNIMIPENEM
    D.3.9.1CAS number 64221-86-9
    D.3.9.2Current sponsor coden.a.
    D.3.9.4EV Substance CodeSUB08151MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number500
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNRELEBACTAM
    D.3.9.2Current sponsor coden.a.
    D.3.9.4EV Substance CodeSUB120519
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number250
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNCILASTATINA
    D.3.9.1CAS number 82009-34-5
    D.3.9.2Current sponsor coden.a.
    D.3.9.4EV Substance CodeSUB06264MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number500
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Piperacillin/Tazobactam-Teva
    D.2.1.1.2Name of the Marketing Authorisation holderTeva GmbH
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product namepipiracillina/tazobactam
    D.3.2Product code [n.a.]
    D.3.4Pharmaceutical form Powder for solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNTAZOBACTAM
    D.3.9.2Current sponsor coden.a.
    D.3.9.4EV Substance CodeSUB10849MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number500
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPIPERACILLINA
    D.3.9.2Current sponsor coden.a.
    D.3.9.4EV Substance CodeSUB09867MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number4000
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 3
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name n.a.
    D.2.1.1.2Name of the Marketing Authorisation holdern.a.
    D.2.1.2Country which granted the Marketing AuthorisationItaly
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameLinezolid
    D.3.2Product code [n.a.]
    D.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNLINEZOLID
    D.3.9.1CAS number 165800-03-3
    D.3.9.2Current sponsor coden.a.
    D.3.9.4EV Substance CodeSUB08520MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 4
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product namepiperacillin/tazobactam
    D.3.2Product code [-n.a.]
    D.3.4Pharmaceutical form Powder for solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNTAZOBACTAM
    D.3.9.2Current sponsor codeN,A,
    D.3.9.3Other descriptive nameTAZOBACTAM
    D.3.9.4EV Substance CodeSUB10849MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number500
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPIPERACILLINA
    D.3.9.2Current sponsor codeN.A.
    D.3.9.3Other descriptive namePIPERACILLINA
    D.3.9.4EV Substance CodeSUB09867MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number4000
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Treatment for hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP).
    Trattamento della polmonite batterica acquisita in ospedale associata a ventilazione (HABP/VABP).
    E.1.1.1Medical condition in easily understood language
    Bacterial Infections
    Infezioni batteriche.
    E.1.1.2Therapeutic area Diseases [C] - Bacterial Infections and Mycoses [C01]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10071097
    E.1.2Term Beta-lactam antibiotic resistance
    E.1.2System Organ Class 100000004862
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To determine the incidence rate of all-cause mortality through Day 28 post-randomization associated with treatment with IMI/REL compared to treatment with PIP/TAZ in subjects diagnosed with HABP/VABP in the modified intention-to-treat (MITT) population.
    Determinare il tasso di incidenza di mortalit¿ per qualsiasi causa fino al Giorno 28 post-randomizzazione associato alla terapia con l¿IMI/REL rispetto alla terapia con PIP/TAZ nei soggetti con diagnosi di HABP/VABP nella popolazione intention-to-treat modificata (Modified Intention-To-Treat, MITT).
    E.2.2Secondary objectives of the trial
    To evaluate the efficacy of IMI/REL versus PIP/TAZ with respect to clinical response at the early follow-up (EFU) visit 7 to 14 days after the end of therapy (EOT) for subjects diagnosed with HABP/VABP in the MITT population.
    Valutare l¿efficacia di IMI/REL rispetto a PIP/TAZ nella risposta clinica alla visita di follow-up precoce (EFU) da 7 a 14 giorni dopo la fine della terapia (EOT) per i soggetti con diagnosi di HABP/VABP nella popolazione MITT.
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives

    Other types of substudies
    Specify title, date and version of each substudy with relative objectives: A Phase III, Randomized, Double-Blind, Active Comparator-Controlled Clinical Trial to Study the Safety, Tolerability, and Efficacy of Imipenem/Cilastatin/Relebactam (MK-7655A) Versus Piperacillin/Tazobactam in Subjects with Hospital-Acquired Bacterial Pneumonia or Ventilator-Associated Bacterial Pneumonia (Future Biomedical Research).
    Merck will conduct Future Biomedical Research on DNA (blood) specimens collected during this clinical trial. Such research is for biomarker testing to address emergent questions not described elsewhere in the protocol (as part of the main trial) and will only be conducted on specimens from appropriately consented subjects. The objective of collecting specimens for Future Biomedical Research is to explore and identify biomarkers that inform the scientific understanding of diseases and/or their therapeutic treatments. The overarching goal is to use such information to develop safer, more effective drugs, and/or to ensure that subjects receive the correct dose of the correct drug at the correct time.

    Altre tipologie di sottostudi
    specificare il titolo, la data e la versione di ogni sottostudio con i relativi obiettivi: Studio clinico di fase III, randomizzato, in doppio cieco, controllato con farmaco attivo di confronto per valutare la sicurezza, la tollerabilit¿ e l¿efficacia di Imipenem/Cilastatina/Relebactam (MK7655A) verso Piperacillina/Tazobactam in pazienti affetti da polmonite batterica nosocomiale o associata a ventilazione meccanica.
    Merck condurr¿ una Ricerca Biomedica Futura su campioni di DNA (estratti dal sangue) raccolti nel corso di questo studio clinico.
    Tale ricerca ha lo scopo di esaminare vari biomarcatori per rispondere a domande che stanno emergendo e che non sono descritte in altre parti del protocollo (nell¿ambito dello studio principale), e verr¿ condotta solo su campioni di soggetti che abbiano rilasciato apposito consenso. L'obiettivo della raccolta dei campioni per la Ricerca Biomedica Futura ¿ quello di esplorare e identificare biomarcatori che contribuiscano scientificamente alla comprensione delle malattie e/o della relative terapie. L'obiettivo ultimo ¿ quello di utilizzare tali informazioni per sviluppare farmaci pi¿ sicuri e pi¿ efficaci, e/o per garantire che i soggetti ricevano la dose giusta del giusto farmaco al momento giusto.
    E.3Principal inclusion criteria
    1. be = 18 years of age on the day of signing informed consent. 2. require treatment with IV antibiotic therapy for hospital-acquired bacterial pneumonia (HABP) or ventilator-associated bacterial pneumonia (VABP). 3. fulfill the clinical and radiographic criteria (detailed in the protocol) with onset of criteria occurring after more than 48 hours of hospitalization or within 7 days after discharge from a hospital (for HABP) or at least 48 hours after mechanical ventilation (for VABP): Refer to protocol for defining clinical features. 4. have a baseline (at or within 48 hours of screening) lower respiratory tract specimen obtained for Gram stain and culture. 5. have an infection known or thought to be, in the opinion of the investigator, caused by microorganisms susceptible to the IV study therapy. 6. agree to allow any bacterial isolates obtained from protocol-required specimens related to the current infection to be provided to the Central Microbiology Reference Laboratory for study-related microbiological testing, long-term storage, and other future testing. 7. understand (or have a legal representative that understands) the study procedures, alternative treatments available, and risks involved with the study, and voluntarily agree to participate by giving written informed consent for the trial. The subject may also provide consent for Future Biomedical Research. However, the subject may participate in the main trial without participating in Future Biomedical Research. 8. if male or female of childbearing potential, use appropriate contraception (refer to protocol for contraception guidance details).
    1. avere = 18 anni d’età il giorno in cui firma il consenso informato.
    2. richiedono terapia antibiotica per via EV per polmonite batterica nosocomiale (HABP) o polmonite batterica da ventilazione meccanica (VABP).
    3. soddisfano i criteri clinici e radiografici di seguito descritti, con insorgenza di criteri che si verificano dopo più di 48 ore di ospedalizzazione o entro 7 giorni dalla dimissione da un ospedale (per HABP) o almeno 48 ore dopo la ventilazione meccanica (per VABP). Si veda il protocollo per dettagli.
    4. avere adeguati campioni al basale (entro 48 ore dallo screening) delle basse vie respiratorie ottenuti per colorazione e coltura di Gram.
    5. presentano infezioni che, secondo secondo l’opinione dello sperimentatore, si ritiene che o è noto che sono causate da ceppi di microorganismi suscettibili alla terapia di studio per via EV.
    6. accettare di permettere che gli isolati batterici correlati all’infezione in corso ottenuti dai campioni richiesti dal protocollo siano forniti al Laboratorio microbiologico centrale di riferimento per le analisi microbiologiche relative allo studio conservazione a lungo termine e altre analisi future.
    7. comprendere (o avere un rappresentante legale che comprenda) le procedure dello studio, i trattamenti alternativi disponibili e i rischi correlati allo studio e acconsentire volontariamente a partecipare fornendo il consenso informato scritto alla sperimentazione. Il soggetto può inoltre decidere di fornire il consenso per la ricerca biomedica futura. Tuttavia, il soggetto può partecipare alla sperimentazione principale senza prendere parte alla Ricerca biomedica futura.
    8. Se uomo o donna in età fertile, utilizza metodi contraccettivi accettabili.
    E.4Principal exclusion criteria
    1.has a baseline lower respiratory tract specimen Gram stain that shows the presence of Gram-positive cocci only. 2. has confirmed or suspected community-acquired bacterial pneumonia (CABP). 3. has confirmed or suspected pneumonia of viral, fungal, or parasitic etiology. 4. has HABP/VABP caused by an obstructive process, including lung cancer (or other malignancy metastatic to the lungs resulting in pulmonary obstruction) or other known obstruction. 5. has a carcinoid tumor or carcinoid syndrome. 6. has active immunosuppression, defined as either receiving immunosuppressive medications or having a medical condition associated with immunodeficiency. 7. is expected to survive < 72 hours. 8. has a concurrent condition or infection that, in the investigator’s judgment, would preclude evaluation of therapeutic response (e.g. active tuberculosis, cystic fibrosis, granulomatous disease, a disseminated fungal infection, invasive fungal pulmonary infection or endocarditis). 9. has received effective antibacterial drug therapy for the index infection of HABP/VABP for a continuous duration of more than 24 hours during the previous 72 hours. 10. a history of serious allergy, hypersensitivity (e.g., anaphylaxis), or any serious reaction to any of the following: any penicillin or ß-lactamase inhibitors. 11. is a female who is pregnant or is expecting to conceive (or is a male partner of a female who is expecting to conceive), is breastfeeding, or plans to breastfeed prior to completion of the study. 12. has a history of a seizure disorder which has required ongoing treatment with anti-convulsive therapy or prior treatment with anti-convulsive therapy within the last 3 years. 13. is anticipated to be treated with any of the following medications during the course of study therapy: refer to ptorocol for list on concomitant meds 14. has an estimated or actual creatinine clearance of < 15 mL/min at screening, based on the findings of local laboratory values. 15. is currently undergoing hemodialysis or peritoneal dialysis. 16. has a history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that, in the opinion of the investigator, might confound the results of the study, interfere with the subject’s participation for the full duration of the study, or pose additional risk in administering the study drugs to the subject.
    1. la colorazione di Gram del campione delle basse vie respiratorie mostra solo la presenza di cocchi Gram-positivi.
    2. ha una polmonite batterica acquisita in comunità (Community-Acquired Bacterial Pneumonia, CABP) confermata o sospetta.
    3. ha polmonite confermata o sospetta con eziologia virale, fungina o parassitaria.
    4. presenta una HABP/VABP causata da un processo ostruttivo, tra cui tumore polmonare (o altra neoplasia maligna metastatica ai polmoni che causi ostruzione polmonare) o altra ostruzione nota.
    5. presenta un tumore carcinoide o sindrome da carcinoide.
    6. presenta immunosoppressione attiva, definita sia come l’assunzione di farmaci immunosoppressivi o che ha una condizione medica associata ad immunodeficienza.
    7. ci si attende che sopravviva < 72 ore.
    8. ha una condizione concomitante o infezione che, a giudizio dello sperimentatore, impedirebbe la valutazione della risposta terapeutica (ad es. tubercolosi attiva, fibrosi cistica, malattia granulomatosa, infezione fungina disseminata, infezioni polmonari fungine invasive o endocardite).
    9. ha ricevuto un farmaco antibatterico per la HABP/VABP per un periodo continuativo superiore alle 24 ore nelle precedenti 72 ore.
    10. ha un’anamnesi di allergia grave, ipersensibilità (ad es. anafilassi) o reazione grave a qualsiasi dei seguenti: qualunque penicillina o inibitori delle ß-lattamasi
    11. è una donna in stato di gravidanza o che prevede di concepire (o è il partner maschile di una donna che prevede di concepire), che sta allattando o che prevede di allattare prima del completamento dello studio.
    12. ha un’anamnesi di disturbo convulsivo che richieda un trattamento in corso con terapia anticonvulsivante o abbia richiesto un precedente trattamento con terapia anticonvulsivante negli ultimi 3 anni.
    13. prevede di essere trattato con uno qualsiasi dei seguenti farmaci nel corso della terapia dello studio:si faccia riferimento al protocollo
    14. ha una clearance della creatinina stimata o reale di < 15 ml/min allo screening in base ai risultati dei valori del laboratorio locale.
    15. è attualmente sottoposto/a a emodialisi o a dialisi peritoneale.
    16. presenta un’anamnesi o un’evidenza attuale di qualsiasi condizione, terapia, valore anormale di laboratorio o altra circostanza che, a giudizio dello sperimentatore, potrebbe inficiare i risultati dello studio, interferire con la partecipazione del soggetto per l’intera durata dello studio o comportare un rischio aggiuntivo nella somministrazione dei farmaci in studio al soggetto.
    E.5 End points
    E.5.1Primary end point(s)
    Survival/All-cause Mortality: Survival status
    (i.e., whether the subject is alive or dead) through Day 28 post-randomization and EFU visits will be evaluated for all subjects in
    support of the primary and key secondary objectives, respectively.
    Sopravvivenza/ mortalità da tutte le cause: stato di sopravvivenza (un soggetto è vivo o è deceduto) fino al Giorno 28 post-randomizzazione, e le visite di follow-up precoce (EFU) saranno valutate per tutti i soggetti a supporto degli obiettivi primari e secondari chiave, rispettivamente.
    E.5.1.1Timepoint(s) of evaluation of this end point
    1. Survival/All-cause Mortality: Day 28.
    1. Sopravvivenza/mortalità per qualsiasi causa: Giorno 28.
    E.5.2Secondary end point(s)
    Clinical response will be assessed for all subjects based on evaluation by the investigator at the OTX1, OTX2, OTX3 (if applicable), EOT, EFU, and Day 28 postrandomization visits. Microbiological response will be evaluated separately for each lower respiratory tract pathogen isolated in the baseline culture (i.e., by-pathogen). The by-pathogen response rating determined by the investigator will be assessed based on local laboratory results.
    La risposta clinica verr¿ valutata su tutti i soggetti sulla base della valutazione dello sperimentatore ad OTX1, OTX2, OTX3 (se applicabile), EOT, EFU, ed alla visita del giorno 28 post-randomizzazione. La risposta microbiologica sar¿ valutata separatamente per ciascun patogeno isolato al basale dal basso tratto respiratorio. Il tasso di risposta per-patogeno determinato dallo sperimentatore verr¿ valutatto sulla base dei risultati delle analisi fatte dal laboratorio locale.
    E.5.2.1Timepoint(s) of evaluation of this end point
    1. Clinical response: OTX1, OTX2, OTX3 (if applicable), EOT, EFU, and Day 28 post-randomization visits.
    2. Microbiological response: EOT & EFU.
    1. Risposta clinica: OTX1, OTX2, OTX3 (se applicabile), EOT, visite EFU, e giorno 28 dopo la randomizzazione.
    2. Risposta microbiologica: EOT & EFU.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Yes
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned5
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA50
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA Information not present in EudraCT
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Argentina
    Australia
    Brazil
    Bulgaria
    Canada
    Colombia
    Croatia
    Czechia
    Estonia
    France
    Georgia
    Germany
    Guatemala
    Italy
    Japan
    Korea, Republic of
    Latvia
    Lithuania
    Mexico
    Norway
    Peru
    Philippines
    Portugal
    Romania
    Russian Federation
    Serbia
    Spain
    Turkey
    Ukraine
    United States
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months2
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months2
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 430
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 106
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Mechanically ventilated patients.
    Pazienti ventilati meccanicamente.
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state6
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 161
    F.4.2.2In the whole clinical trial 536
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Subjects who discontinue/withdraw from IV study therapy prior to completion of the IV study therapy regimen should continue to be followed for all remaining study visits. When a subject discontinues/withdraws from participation in the trial, all applicable activities scheduled for the final trial visit should be performed at the time of discontinuation. Any adverse events which are present at the time of discontinuation/withdrawal should be followed until resolution.
    I soggetti che interrompono/si ritirano dalla terapia endovenosa in studio prima della fine della stessa, devono continuare ad essere seguiti per tutte le restanti visite dello studio. Quando un soggetto interrompe/ritira la partecipazione allo studio, tutte le attivit¿ previste alla visita finale devono essere eseguite al momento dell¿interruzione. Eventuali eventi avversi che sono presenti al momento della sospensione/ritiro devono essere seguiti fino alla risoluzione.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2015-11-27
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-12-15
    P. End of Trial
    P.End of Trial StatusCompleted
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
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